The cornea protects the intraocular contents and serves as major optical element of the eye. 75% of the diopteric power of the eye depends on the interface of the cornea and air. Injury, disease or cellular failure can cause opacification of the cornea with subsequent impairment and corneal blindness. Affecting more than 10 million patients worldwide, corneal opacification is often managed by transplantation of human donor tissues. This procedure has a poor success rate in disorders such as autoimmune conditions or chemical injuries. In industrialized countries, the ageing of the population exacerbates this demand, which is compounded by the shelf-life of donated eyes being only a few days. Furthermore, in developing countries where the number of cases of cornea blindness is increasingly problematic, healthy donor tissue is rare. Alternatively, corneal transplants are needed in several third world countries where donor corneas are not culturally acceptable. Multiple models and devices are necessary to accommodate the various pathological states of the corneas.
Polymers and Corneal Implants
Many attempts have been made to create artificial corneas or keratoprostheses in order to replace donor cornea grafts. Such attempts have often failed because of an absence of healing and permanent attachment between the periphery of the synthetic device and the residual rim of the host cornea. As a result, tissue necrosis, leakage of aqueous humor, epithelial down-growth, and intraocular infection frequently occur occurred.
Numerous keratoprostheses have been developed using a variety of polymer materials such as poly-(2-hydroxy ethyl methacrylate) (pHEMA), poly-(methyl methacrylate), polyvinyl alcohol, or poly-(ethyl vinyl alcohol), and in some instances mixed with collagen or hyaluronic acid, (Chirila, 2001; U.S. Pat. No. 5,458,819 (Chirila et al., issued Oct. 17, 1995); U.S. Pat. No. 5,300,116 (Chirila et al., issued Apr. 5, 1994); Hicks et al., 1998a; 1998b; Guisti et al., 1994, Legais et al., 1995; 2001; Legeais and Renard, 1998, Robert et al., 2001; Trinskaus-Randell et al., 1988; 1997; Trinskaus-Randell and Nugent, 1998; Vijayasekaran et al., 1998; 2000; Wu et al., 1998; U.S. Pat. No. 5,436,135 by Tayot et al; Jul. 25, 1995). Most keratoprostheses in development consist of a central transparent optical element, surrounded by a porous opaque material as a peripheral rim that allows penetration and proliferation of stromal keratocytes and the subsequent synthesis of collagen within the material. The peripheral rim has been made of different polymers such as polybutylene-polypropylene, and expanded poly(tetrafluoroethylene). U.S. Pat. No. 6,005,160 (Hsiue et al; Dec. 21, 1999) describes a heterofunctional membrane for application as an artificial cornea using polyacrylic acid or polymethacrylic acid, and then bonded with collagen, or HEMA, or with polyethylene oxide. A hetero, bi-functional biomedical surface can also be developed with 2-methacryloyloxyethyl phosphorylcholine, or 2-methacryloyloethyl phosphorylcholine. Such a product has good transparency, hydrophilicity and high biocompatibility. These devices have been more or less successful (e.g., remain in place for 6 months). However, the skirt of most of them have low tensile strength leading to suturability problems, inflammatory reaction, and subsequent extrusion of the keratoprosthesis. A keratoprosthesis made of a transparent pHEMA core is undergoing clinical trials (Chirila et al., 2001).
Other corneal implants have been designed to correct the cornea curvature by inserting an intrastromal implant using polymers in a form of microporous hydrogel material. However, extrusion is still a major issue, as it is undesirable because it tends to cause clinical complications and product failure. For example, a polymerized PEG (by gamma radiation) hydrogel has been designed to be injectable into the stroma (U.S. Pat. No. 6,102,946 by Nigam A, issued Aug. 15, 2000). U.S. Pat. No. 5,994,133 (Meijs et al; Nov. 30, 1999) reports a corneal implant made with macromonomer of perfluoropolyether. U.S. Pat. No. 4,702,244 (Mazzocco; Oct. 27, 1987) reports a polyurethane/collagen hydrogel compound for an intraocular artificial lens. US patent application 20010018612 (Carson DR, published Aug. 30, 2001) describes an intraocular lens for long term implantation in the cornea composed of two hydrogel materials made of copolymer of N-vinyl-pyrrolidone and 2-phenylethyl methacrylate and the second polymer is based on glyceryl methacrylate.
Biological and Cell-Seeded Materials
Human amniotic membrane can be used as replacement for full-thickness corneal defects. Although, corneal architecture is normally restored at long term with a layering of the epithelium and endothelium, with pigmentation and vascularization present in the deep layers of the cornea, amniotic membranes are susceptible to infectious contamination and transmission. Type IV collagen from placenta has been proposed to replace amniotic membranes (U.S. Pat. No. 5,436,135 (Tayot et al; Jul. 25, 1995)). U.S. Pat. No. 5,114,627 (Civerchia; May 19, 1992) describes a collagen hydrogel for promoting epithelial cell growth.
Collagen film or hydrogels can be used as cornea dressing or contact lens (Miyata et al., 1992). Most collagen materials have been chemically crosslinked to increase their resistance to biodegradation.
Alternatively, attempts have been made to reconstruct corneas in vitro from cell lines. Individual human corneal epithelial layers have been successfully maintained in culture as a stratified epithelium (Kahn et al., 1993; Araki-Sasaki et al., 1995). Successful reconstructions of corneas comprising the 3 main layers have also been reported using animal cells (Minami et al., 1993; Zieske et al., 1994), and more recently, a whole human cornea equivalent was reconstituted with biological polymers and cells that mimics the physiology of the human cornea and surrounding tissue (Griffith et al., 1999; Griffith et al., published international application PCT/CA99/00057 [published Jul. 29, 1999 as WO 99/37752]). PCT/CA99/00057 relates to reconstruction of in vitro cell-based models for use as animal alternatives in irritancy, toxicity, and drug efficacy testing.
There thus remains a great need for improved materials and systems for use in corneal implants, repair and transplantation.